PTEN (phosphatase and tensin homologue deleted on chromosome ten)is a tumor suppressor gene having both protein and lipid phosphatase activity. By its lipid phosphatase activity, it catalyzes dephosphorylation of D3 position of the myo-inositol ring of phosphatidylinositides, and thus counteracts the activity of phosphatidylinositol 3-kinase (PI3K). Our goal is to understand the role of PTEN in T cell activation. Our preliminary data indicates that PTEN blocks the transcriptional activity mediated by NFkB/Rel family transcription factors. The blockage in transcription is not due to the deficit in either nuclear translocation or the DNA binding of NFkB proteins, but in the transactivation potential of NFkB p65 protein. We are trying to identify the posttranslational modification of p65 protein by PTEN using two-dimentional electrophoresis analysis, which might explain the lack of transactivation potential of p65 in PTEN expressing cells. The second part of this project deals with the role of PTEN in T cell proliferation. Based on our preliminary data, we are investigating the role of PTEN as a cell cycle blocker at G0/G1 transition.